The objective of this research project is to investigate the physiogenetic basis of lymphopoiesis and to study the immunological and pathological characteristics in the high (HLC) and low leukocyte count (LLC) lines of mice. The HLC and LLC mice are developed by selective breeding for differences in leukocyte production. As a result of selection they differ in biological and immunological characteristics and in development of pahtological conditions in addition to a 6- to 7-fold difference in leukocyte counts. We are making linkage studies and attempting to identify individual genes on different chromosomes which exert a significant effect on leukocyte production. For immunological studies, we are testing for differences in response to different antigens and carcinogens, and in proportion of T-lymphocytes and B-lymphocytes between the HLC and LLC mice. For pathological studies, we are making statistical comparisons between these lines in the incidence of neoplasia incidences, and making both light and microscopic examinations of amyloid which occurs in about 100 per cent of LLC mice. We are using both immunochemical procedures and electron microscopy, searching for the origin of amyloid fibril protein. The effect of the differences in leukocyte counts on tissue transplantation and graft-versus-host reaction will be studied when the mice attain a high level of inbreeding. Eventually, we will attempt to establish the cause and effect relationship for biological, immunological, and pathological characteristics in these lines of mice. BIBLIOGRAPHIC REFERENCES: Chai, C.K. 1976. Genetic Evolution. University of Chicago Press, Chicago Ill., in press. Chai, C.K. 1976. Reticular cell hyperplasia and amyloidosis in a line of mice with low leukocyte counts. Amer. J. Path., in press.